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P19784 (CSK22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Casein kinase II subunit alpha'

Short name=CK II alpha'
EC=2.7.11.1
Gene names
Name:CSNK2A2
Synonyms:CK2A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length350 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Ref.3 Ref.4 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization By similarity.

Subunit structure

Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1. Ref.3 Ref.5

Miscellaneous

Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Transcription
Transcription regulation
Wnt signaling pathway
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

axon guidance

Traceable author statement. Source: Reactome

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic spindle checkpoint

Inferred from mutant phenotype Ref.4. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 21282530. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein N-terminus binding

Inferred from physical interaction PubMed 11972058. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10094392PubMed 14667819PubMed 19011756PubMed 21988832PubMed 23455922PubMed 23555304. Source: IntAct

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 350350Casein kinase II subunit alpha'
PRO_0000085891

Regions

Domain40 – 325286Protein kinase
Nucleotide binding46 – 549ATP By similarity

Sites

Active site1571Proton acceptor By similarity
Binding site691ATP By similarity

Amino acid modifications

Modified residue131Phosphotyrosine Ref.14
Modified residue181Phosphoserine Ref.8 Ref.14
Modified residue211Phosphoserine Ref.8 Ref.14
Modified residue971N6-acetyllysine Ref.15
Modified residue2881Phosphoserine Ref.8 Ref.14

Natural variations

Natural variant1881E → A. Ref.19
Corresponds to variant rs55911801 [ dbSNP | Ensembl ].
VAR_040416

Secondary structure

.............................................................. 350
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P19784 [UniParc].

Last modified February 1, 1991. Version 1.
Checksum: 3ECB92F6BD3DD7F1

FASTA35041,213
        10         20         30         40         50         60 
MPGPAAGSRA RVYAEVNSLR SREYWDYEAH VPSWGNQDDY QLVRKLGRGK YSEVFEAINI 

        70         80         90        100        110        120 
TNNERVVVKI LKPVKKKKIK REVKILENLR GGTNIIKLID TVKDPVSKTP ALVFEYINNT 

       130        140        150        160        170        180 
DFKQLYQILT DFDIRFYMYE LLKALDYCHS KGIMHRDVKP HNVMIDHQQK KLRLIDWGLA 

       190        200        210        220        230        240 
EFYHPAQEYN VRVASRYFKG PELLVDYQMY DYSLDMWSLG CMLASMIFRR EPFFHGQDNY 

       250        260        270        280        290        300 
DQLVRIAKVL GTEELYGYLK KYHIDLDPHF NDILGQHSRK RWENFIHSEN RHLVSPEALD 

       310        320        330        340        350 
LLDKLLRYDH QQRLTAKEAM EHPYFYPVVK EQSQPCADNA VLSSGLTAAR 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of human cDNA clones encoding the alpha and the alpha' subunits of casein kinase II."
Lozeman F.J., Litchfield D.W., Piening C., Takio K., Walsh K.A., Krebs E.G.
Biochemistry 29:8436-8447(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary.
[3]"A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1."
Keller D.M., Zeng X., Wang Y., Zhang Q.H., Kapoor M., Shu H., Goodman R., Lozano G., Zhao Y., Lu H.
Mol. Cell 7:283-292(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SSRP1 AND SUPT16H.
[4]"Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells."
Sayed M., Pelech S., Wong C., Marotta A., Salh B.
Oncogene 20:6994-7005(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL CYCLE.
[5]"p53 serine 392 phosphorylation increases after UV through induction of the assembly of the CK2.hSPT16.SSRP1 complex."
Keller D.M., Lu H.
J. Biol. Chem. 277:50206-50213(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SSRP1 AND SUPT16H.
[6]"Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8."
Shin S., Lee Y., Kim W., Ko H., Choi H., Kim K.
EMBO J. 24:3532-3542(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS.
[7]"One-thousand-and-one substrates of protein kinase CK2?"
Meggio F., Pinna L.A.
FASEB J. 17:349-368(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[8]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-21 AND SER-288, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights."
Niefind K., Raaf J., Issinger O.G.
Cell. Mol. Life Sci. 66:1800-1816(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON STRUCTURE.
[10]"Protein kinase CK2 in health and disease: From birth to death: the role of protein kinase CK2 in the regulation of cell proliferation and survival."
St-Denis N.A., Litchfield D.W.
Cell. Mol. Life Sci. 66:1817-1829(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[11]"Protein kinase CK2 in health and disease: Cellular functions of protein kinase CK2: a dynamic affair."
Filhol O., Cochet C.
Cell. Mol. Life Sci. 66:1830-1839(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[12]"Protein kinase CK2 in health and disease: CK2: the kinase controlling the Hsp90 chaperone machinery."
Miyata Y.
Cell. Mol. Life Sci. 66:1840-1849(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN REGULATION OF HSP90.
[13]"Protein kinase CK2 in health and disease: CK2 and its role in Wnt and NF-kappaB signaling: linking development and cancer."
Dominguez I., Sonenshein G.E., Seldin D.C.
Cell. Mol. Life Sci. 66:1850-1857(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN WNT SIGNALING.
[14]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-13; SER-18; SER-21 AND SER-288, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor."
Nakaniwa T., Kinoshita T., Sekiguchi Y., Tada T., Nakanishi I., Kitaura K., Suzuki Y., Ohno H., Hirasawa A., Tsujimoto G.
Acta Crystallogr. F 65:75-79(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 1-334 IN COMPLEX WITH INHIBITOR.
[18]"Structure of the human protein kinase CK2 catalytic subunit CK2alpha' and interaction thermodynamics with the regulatory subunit CK2beta."
Bischoff N., Olsen B., Raaf J., Bretner M., Issinger O.G., Niefind K.
J. Mol. Biol. 407:1-12(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS).
[19]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-188.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55268 mRNA. Translation: AAA51548.1.
BC008812 mRNA. Translation: AAH08812.1.
CCDSCCDS10794.1.
PIRB35838.
RefSeqNP_001887.1. NM_001896.2.
UniGeneHs.82201.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3E3BX-ray3.20X1-334[»]
3OFMX-ray2.00A1-350[»]
3U87X-ray2.90A/B327-350[»]
ProteinModelPortalP19784.
SMRP19784. Positions 8-332.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107842. 255 interactions.
DIPDIP-318N.
IntActP19784. 93 interactions.
MINTMINT-5004107.
STRING9606.ENSP00000262506.

Chemistry

BindingDBP19784.
ChEMBLCHEMBL4070.
GuidetoPHARMACOLOGY1550.

PTM databases

PhosphoSiteP19784.

Polymorphism databases

DMDM125266.

2D gel databases

SWISS-2DPAGEP19784.

Proteomic databases

MaxQBP19784.
PaxDbP19784.
PeptideAtlasP19784.
PRIDEP19784.

Protocols and materials databases

DNASU1459.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262506; ENSP00000262506; ENSG00000070770.
GeneID1459.
KEGGhsa:1459.
UCSCuc002enc.3. human.

Organism-specific databases

CTD1459.
GeneCardsGC16M058191.
HGNCHGNC:2459. CSNK2A2.
MIM115442. gene.
neXtProtNX_P19784.
PharmGKBPA26959.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233021.
HOVERGENHBG107282.
InParanoidP19784.
KOK03097.
OMAPSWGNQD.
OrthoDBEOG7QG446.
PhylomeDBP19784.
TreeFamTF300483.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
SignaLinkP19784.

Gene expression databases

ArrayExpressP19784.
BgeeP19784.
CleanExHS_CSNK2A2.
GenevestigatorP19784.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCSNK2A2. human.
EvolutionaryTraceP19784.
GeneWikiCSNK2A2.
GenomeRNAi1459.
NextBio5997.
PROP19784.
SOURCESearch...

Entry information

Entry nameCSK22_HUMAN
AccessionPrimary (citable) accession number: P19784
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: July 9, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM